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Published on: February 8, 2013
Concordant loss of fragile gene expression early in breast cancer development
Gulnur Guler1, Aysegul Uner, Nilufer Guler
1Department of Pathology, Haceteppe University, Ankara, Turkey. gguler@hacettepe.edu.tr
Abstract:
The FHIT and WWOX genes encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3, respectively. Reduced Fhit and Wwox expression has been reported in approximately two-thirds of invasive breast tumors. Expression of these fragile gene products, as well as ErbB2 and p53, were evaluated immunohistochemically in 44 pure and 31 adjacent-to-invasive ductal carcinoma in-situ (DCIS) cases. Reduced Fhit and Wwox expression were observed in (i) 70% and 68% of pure DCIS; (ii) 52% and 55% of DCIS adjacent-to-invasive tumor cases; and (iii) 20% and 50% of adjacent normal tissue in pure DCIS cases. Reduced Wwox expression in adjacent normal tissue was observed in 30% of cases in the DCIS adjacent-to-invasive group. Reduced Fhit and Wwox expression was observed in 61% of adjoining invasive tumors. In all normal, pure DCIS, and DCIS adjacent-to-invasive lesions, Fhit and Wwox expression was positively associated (P = 0.034, P = 0.042, P = 0.004, respectively) and in the invasive component there was a positive trend toward association (P = 0.075). Fhit and Wwox were more frequently reduced in high-grade lesions in the DCIS adjacent-to-invasive (P = 0.025, P = 0.004, respectively). In the pure DCIS group, there was a statistically significant negative association between Fhit and ErbB2 expression in DCIS (P = 0.035). In summary, reduced Fhit and Wwox expression in in-situ breast cancer was associated, which may contribute to the high-grade DCIS-invasive tumor pathway.
Insights
Reduced expression of Fhit and Wwox proteins is common in breast cancer, particularly in high-grade ductal carcinoma in situ (DCIS). This reduced expression is associated with tumor progression and may indicate a pathway toward invasive breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The FHIT and WWOX genes, located at fragile sites FRA3B and FRA16D, are frequently altered in various cancers.
- Reduced expression of Fhit and Wwox proteins has been observed in approximately two-thirds of invasive breast tumors.
- These proteins are considered tumor suppressors, and their loss may contribute to cancer development.
Purpose of the Study:
- To investigate the expression levels of Fhit and Wwox proteins in ductal carcinoma in situ (DCIS) and adjacent normal tissues.
- To determine the association between Fhit and Wwox expression and clinicopathological features of DCIS, including grade and invasiveness.
- To explore the relationship between Fhit/Wwox expression and other relevant markers like ErbB2 and p53.
Main Methods:
- Immunohistochemical analysis was performed on 44 pure DCIS cases and 31 cases of DCIS adjacent to invasive tumors.
- Expression levels of Fhit, Wwox, ErbB2, and p53 proteins were evaluated.
- Statistical analyses were used to assess associations between protein expression, tumor grade, and invasiveness.
Main Results:
- Reduced Fhit and Wwox expression was observed in a significant proportion of pure DCIS (70% and 68%) and DCIS adjacent to invasive tumors (52% and 55%).
- Reduced expression of both proteins was also found in adjacent invasive tumors (61%).
- Fhit and Wwox expression was positively associated in normal tissue, pure DCIS, and DCIS adjacent to invasive lesions. Reduced expression was more frequent in high-grade DCIS adjacent to invasive tumors.
Conclusions:
- Reduced Fhit and Wwox expression is a common event in early-stage breast cancer (DCIS) and is associated with high-grade lesions.
- The coordinated reduction of Fhit and Wwox suggests a potential role in the progression from DCIS to invasive breast cancer.
- These findings highlight the importance of Fhit and Wwox as potential biomarkers in breast cancer development and progression.
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